Henmi Takuya, Matsuoka Hideaki, Katayama Noa, Saito Mikako
Department of Biotechnology and Life Science, Tokyo University of Agriculture and Technology, 2-24-16, Naka-cho, Koganei 184-8588, Tokyo, Japan.
Bioresource Laboratories, Tokyo University of Agriculture and Technology, 2-24-16, Naka-cho, Koganei 184-8588, Tokyo, Japan.
Int J Mol Sci. 2024 Nov 28;25(23):12794. doi: 10.3390/ijms252312794.
It has been demonstrated that cancer cells that have survived cancer treatment may be more malignant than the original cancer cells. These cells are considered the main cause of metastasis in prognosis. A -overexpressing colon-26 (colon26) was generated to obtain such a malignant cancer cell model, which was confirmed by enhancement of metastatic potential by in vivo tests using mice. Extracellular vesicles (EVs) secreted from colon26 cells (colon26EVs) were administered to mice three times per week for three weeks. Subsequently, colon26 cells were administered, and metastatic colonies were analyzed two weeks later. The results demonstrated that the administration of EVs suppressed metastasis. colon26EVs enhanced phagocytic activity and M1 marker CD80 of a macrophage cell line J774.1. These suggested the enforcement of tumor-suppressive properties of macrophages and their contribution to the in vivo suppression of metastasis. Small RNA sequencing was conducted to identify -dependent miRNAs that exhibited significant changes (Fc ≥ 1.5 or Fc ≤ 1/1.5; < 0.05) in colon26EVs relative to colon26EVs. Nine miRNAs (up-regulated: four, down-regulated: five) were identified, and 623 genes were predicted to be their target genes. Of the 623 genes identified, nine genes were predicted to be highly relevant to macrophage functions such as phagocytosis.
已证明，在癌症治疗后存活下来的癌细胞可能比原始癌细胞更具恶性。这些细胞被认为是预后转移的主要原因。通过生成A过表达的结肠26（colon26）细胞来获得这样一种恶性癌细胞模型，这通过使用小鼠进行的体内试验中转移潜能的增强得到了证实。从结肠26细胞分泌的细胞外囊泡（colon26EVs）每周给小鼠给药三次，持续三周。随后，给予结肠26细胞，并在两周后分析转移菌落。结果表明，EVs的给药抑制了转移。结肠26EVs增强了巨噬细胞系J774.1的吞噬活性和M1标志物CD80。这些表明巨噬细胞的肿瘤抑制特性得到增强及其对体内转移抑制的作用。进行了小RNA测序，以鉴定相对于结肠26EVs在结肠26EVs中表现出显著变化（Fc≥1.5或Fc≤1/1.5；P<0.05）的依赖于的miRNA。鉴定出9种miRNA（上调：4种，下调：5种），并预测623个基因是它们的靶基因。在鉴定出的623个基因中，9个基因被预测与吞噬作用等巨噬细胞功能高度相关。
